When the Medicare Part D benefit was constructed, drugs for weight loss were explicitly excluded from coverage, as the limited effectiveness and unfavorable safety profile of medications available at the time failed to justify coverage of drugs perceived to be used for cosmetic purposes. In recent years, drugs activating the glucagon-like peptide-1 receptor (GLP-1R) pathway have proved to achieve significant reductions in body weight with a favorable safety profile. The effectiveness of GLP-1R agonists in reducing weight and improving the metabolic profile warrants the reconsideration of the historical exclusion of weight loss drugs from Part D coverage. In this perspective, we outline policy options to enable Part D coverage of GLP-1R agonists. These include legislative change through the passage of the Treat and Reduce Obesity Act and evaluation of coverage policies under the waiver authority of the Center for Medicare and Medicaid Innovation.